Nilotinib is reasonably safe and may halt the disease progression in moderately severe Parkinson's disease patients

Abstract

The primary objective was nilotinib safety and tolerability in moderately severe PD patients, in this phase II study. An exploratory objective is to assess nilotinib effects on motor and non-motor symptoms at baseline, 6, 12 and 15 months. Participants had PD, with a MDS-UPDRS-III motor score 20-40, and MoCA ≥22. 75 participants were randomized 1:1:1 into placebo, 150mg and 300mg nilotinib oral, once daily for 12 months. 88% of participants completed the treatment and there were no drop-outs due to lack of drug tolerability. Niltonib was found to be reasonably safe with no suspected drug related adverse effects. There was no QTc prolongation or myelosuppression. No differences were observed in MDS-UPDRS-I within and between all study groups tested by a single rater. All groups showed a significant decline in MDS-UPDRS-II scores between baseline and 12 months and after washout. All groups slightly improved on MDS-UPDRS-III motor between baseline and 6 months. The placebo and the 300 mg nilotinib groups remained stable at 12 months and after washout but there was a significant improvement in MDS-UPDRS-III score between baseline and 15 months in the 150 mg nilotinib group (-2.82 points, 95% CI, -4.75- -0.89). No significant differences between each visit were observed in MDS-UPDRS-IV. No statistically significant differences in MDS-UPDRS measurements were observed between groups. There were no statistically significant differences in PDQ-39 between groups, but the placebo group significantly deteriorated after 6 months, while the nilotinib groups did not change. In conclusion these exploratory measures show no clinical worsening in MDS-UPDRS in the nilotinib groups compared to the placebo group that worsened after 6 months of treatment. Taken together, our results will guide the future development of a definitive phase III study to evaluate the effects of nilotinib in PD.